As Rolfers, there is such a variety of information that we get drawn to bringing into our practice. Events on the molecular level are where we effect change, even if we are unable to describe those actions. Biochemistry is a wonderful world of exciting interactions, and the more awareness we have around the cellular experience, the more sensitivity we have about the actual events taking place in our offices.

Membranes are very interesting and are critical to cellular life. They are what separate the inside from the outside; but that is only the beginning of what they do in life. They are intimately involved in energy production, nerve impulse transmission, muscle contraction and hormone production – to name a few. The story of what membranes actually are is fascinating. They are not walls; they are dynamic, selectively permeable and remarkably vibrant.

IN THE BEGINNING…

When the earth was young, and biological life was simply an idea, all that there was included atomic solids, liquids and gases in what is termed the “primordial soup”. It is in this soup that the components of life began to find each other. Within the liquid component of molecular mush, two distinct layers formed – oil and water. The water contained the possibilities of proteins and nucleic acids (leading to DNA), forming through random and consistent encounters. Yet it is the formation of membranes that really got the show of life started, the separation of this and that, the beginning of the inside being distinct from the outside.

Water is a polar molecule, due to its shape on an atomic level. The oxygen side of it is slightly negatively charged while the hydrogens are slightly positive. It is this little magnetic quality that makes water our biological base. Water allows other substances to become dissolved within it, being gently pulled apart by this magnet and creatingopportunities for chemical interaction, which is the basis of our cellular space.

It is the organization of the liquid oil layer in relation to water that brought about the ability to form membranes. Any substance that is liquid and not polar cannot mingle in the water; it forms its own layer, which we commonly call oil. On the molecular level oil is made of hydrocarbon molecules, which are exactly as the name suggests: hydrogen and carbon. These two form many different combinations, with the carbon being the backbone of any length of a chain and the hydrogen filling the electron needs of balance. Together they are neutral in charge, which makes them unable to mix with water – perfect to form a boundary between two pools of water.

LIKE OIL AND WATER

As we all know, when water and oil are mixed together, the oil floats on top due to the fact that it is less dense compared to the water, as well as to its neutral tendency to repel itself from water. How then could it form a thin layer such as a membrane within the biological cellular water? The answer is in the soup.

When the primordial soup had progressed enough to have some molecular shape, the identity of some important compounds started to emerge consistently. Those hydrocarbon molecules (also called lipids) were rewarded for binding themselves with a small polar group on one end (Usually a phosphate molecule). This allowed that one end to mingle with water because of its polar nature. The polar group seems like a head in the water while the hydrocarbon is like a tail still being repelled away. When many of these molecules find themselves together they can form a spherical bubble in water. The polar heads interface with water and the non-polar tails stick together in an organized oil bubble. This is the beginning of a membrane.

Imagine that newly formed spherical bubble getting larger by accumulating more of the same molecules in water, it would naturally flatten. Perhaps even this now flat layer would wrap around and find itself enclosing a microscopic amount of water. Voila! A membrane is born. Moreover, a cellular space has been created which has separated in from out. This is where we began.

In technical terms those hydrocarbon tails are called lipids and they are bound to a phosphate head; thus the whole group is termed a phospholipid. Commonly there are two hydrocarbon lipids bound to a single phosphate in a typical membrane. Also in a typical membrane there are the two layers of phospholipids – one in contact with the outside of a cell, the other in contact with the inside. This biochemical model of a membrane is called the phospholipids bilayer, also termed the fluid mosaic model.

FLUID BARRIER

The fluid aspect of the membrane is intriguing. One might expect a membrane to be a continuous wall of some type of material, but that couldn’t be further from the truth when speaking of cellular membranes. Those phospholipids are individual molecules; they float around by the millions to make up one membrane, and they flow amongst themselves like ping-pong balls on water all tight together. Try to get a gumdrop through a bath of ping-pong balls on water, no problem because the size of the gumdrop is much smaller and therefore can pass through. Take a basketball and it won’t pass through without hugely disrupting the ping-pong ball mosaic. That would essentially punch a hole in our ping-pong ball membrane, which is not what happens in life – those large molecules are kept out. If a cell requires those large molecules, it will have a means to bring them in as needed; this will be discussed further on in this article.

As you can now get a feel for, a cellular membrane is selectively permeable to what can cross through to the other side. In this movement, size is everything. Water is a small molecule relative to the other biological molecules and therefore can pass through a membrane easily. Oxygen and carbon dioxide are both small and pass through a membrane with ease. Glucose and sucrose (sugars needed by cells for en-ergy) are too large to pass through on their own. Proteins, including hormones, are large and cannot simply pass through. Some atoms are also unable to pass through a phospholipids bilayer because they have a strong charge and cannot pass through the oil layer by themselves.

POWER OF PROTEINS

Proteins are important in the functional aspects of cellular membranes. Proteins are made of amino acids. There are twenty amino acids and they are assembled together in various orders and lengths like a string of pearls. That string of pearls gets bundled and twisted upon itself until it is a dense mass of amino acids. Amazingly, the specific amino acid chain always folds in the same way when being assembled into its protein. Proteins are very diverse in their function in cellular life; we will focus here only on their role in membranes.

Membranes have proteins embedded in them. Sometimes they are found only protruding on the inside of a cell; sometimes they only protrude on the outside of the cell while some go right through. They manage to interact with the membrane because some amino acids are polar and will be found in the water matrix portion of a protein and some amino acids are non-polar, making them perfect for spanning that hydrocarbon non-polar center of the membrane.

TAKING WHAT WE NEED

Recall how there are molecules (like glucose) and charged atoms (like sodium) that are unable to pass on their own through a phospholipids bilayer. Proteins are the machinery to get the job done. Every cell has a unique protein makeup in its cell membrane; the cell decides for itself what it needs and puts out a protein to make it happen.

The mechanism of bringing a molecule that is too large to pass on its own into the cell, and is needed by the cell, requires a protein that spans the whole membrane. That protein will be large and bulky in comparison to the size of the molecule it is intended to transport across the membrane. A small part of the protein is called the “active site”. The active site is where the protein receives the molecule it is to transport. Active sites are the perfect shape to bind that molecule (also called a ligand). Once the protein has bound to the ligand, the new molecular configuration initiates a change in the shape of the protein. That change requires energy, which is provided by the inside of the cell. The result of that change in shape involves the protein pulling the ligand to the inside of the cell membrane. Once there, the active site releases the molecule to the inside of the cell. Then the protein resets and has its active site again at the ready on the outside of the cell waiting until another of the same molecule binds. This is called Active Transport and this mechanism is used in many different cellular tissues.

NERVE SIGNAL TRANSMISSION

Let’s examine nerve impulse transmission, which requires the active transport of charged atoms to maintain a charge gradient in resting nerve cells. Specifically, let’s use peripheral nerve cells as an example where we can look at how a signal is transmitted along the axon of a nerve cell by using the inside/ outside differentiation of a membrane and the power of proteins.

As mentioned, a resting nerve cell axon has a charge gradient. This is where the inside of the cell is negatively charged while the outside of the cell is positively charged. This charge is due to a difference in charged atoms, specifically potassium (K+) and sodium (Na+), that both have a single positive charge. The protein that actively transports these two atoms is called the sodiumpotassium exchange pump.

This pump is a variation of the general active transport protein described above; it has five active sites for these charged atoms and a sixth for the energy required to move them through the membrane. Three active sites are found on the inside of the cell which perfectly bind three sodium atoms, whereas there are two active sites on the outside of the cell that perfectly bind two potassium atoms. Once all five charged particles are bound to the protein, along with the energy molecule inside the cell, then the protein morphs, changing shape, and pulling those three sodium to the outside of the cell and the two potassium to the inside. Once done, the protein resets and is ready to do the same action again.

Strangely enough, it is the moving of these positively-charged ions that makes the charge gradient of a resting nerve cell. Since there are more positive ions being pumped into the outer cellular space than the inside, it leaves the outside with a positive charge and the inside of the cell negatively charged, relative to one another. Specifically, there is a membrane potential of 70 millivolts generated by the action of this protein pump. Before we continue, we need to introduce another form of membrane protein, which participates in the transmission of a nerve cell signal.

CHANNELS ARE FOR IONS

Another need of the cell is to move those charged atoms, which are also called ions, through the membrane quickly, and it sometimes makes sense to have a hole open up to expedite the process. There are proteins that are shaped like thick doughnuts through the membrane, which have a pore in the center of them. They are called Ion Channels and they have an interesting function.

It would be detrimental for a cell to have a permanent hole in its membrane, therefore these ion channels are regulated and are able to open and close as the cellular circumstances dictate. Ion channels are used in many different situations throughout a living being. There are several different kinds of ion channels and differing ways for an ion channel to be opened. They mostly stay closed.

A resting ion channel has a gate covering that pore through the center, which blocks everything from passing through. The reason it might open comes from the protein receiving a signal to open. The protein can have an active site on the outside of the cell, to which a signaling molecule binds and opens the gate to the pore. The active site can also be on the inside of the cell, to which the signal would come from the cell. Either way, that pore is also selective and will only allow the passage of a specific atom.

In the example of nerve signal transmission, ion channels are very important. As we already covered, a resting nerve cell has a charge gradient established and maintained by the sodium-potassium pump. When that nerve cell receives a stimulus, there is a signal to sodium ion channels and the potassium ion channels to open. Opening a pore to those positively charged atoms means they will rush across to the other side of the membrane like water over a waterfall. This action is called membrane depolarization. It is this depolarization of the membrane, which is the actual signal that travels the distance of an axon towards the central nervous system or from the central nervous system.

Imagine a sensory nerve axon that runs from a person’s big toe to their spinal cord. A Rolfer contacts that person’s big toe, which causes the ion channels immediately beside that contact to open. The ion channels then open like a series of dominoes being knocked open, once a neighbor ion channel opens, then the next will open, then the next – all traveling at quite a speed up the leg of the person to their spinal cord. It is like a wave rushing up the leg. The front of the wave is the ion channels that are fresh to open, where right behind it in the wake of this molecular movement, channels are closing up just as quick as they opened.Sodium-potassium pumps go to the work of establishing the charge gradient to reset that nerve axon, which they do with incredible efficiency. That moment of membrane depolarization is the signal, the language of our nervous system.

<img src=’https://novo.pedroprado.com.br/imgs/2005/701-1.jpg’>

WHAT ABOUT HORMONES?

Some hormones are proteins; some hormones are a derivative of cholesterol. For the ones that are proteins, they are a specific string of amino acids all wrapped up to make an active hormone. In the examples above, membrane proteins had an active site, which was like a keyhole to which the ligand was the key; hormones have an active site, which is more like a key lookingfor its matching lock. When that hormone key locates the other protein with the matching active site, important events required by the body will take place. Those receiving proteins with the active site for the hormones are commonly found in membranes.

A membrane protein that is simply waiting for its matching hormone to find it is called a receptor. Hormones are circulating in many different fluids in the body; some are found in the blood, some are in the interstitial fluid, some are only found in the synaptic clefts where two nerve cells meet, while others truly move between all these places.

Receptors are located on all cells that are asking to be affected by a particular hormone. Receptors are listening to the chemical environment around the cell, waiting until binding of the matching hormone takes place.Receptors are membrane proteins that span the whole membrane. They have their active sites on the outside of the cell for a specific hormone and when that hormone binds, it stays on the outside of the cell. The amount of time that that hormone remains bound depends on which hormone-receptor pair it is, since they all vary in their properties. When the hormone binds, it causes a change that happens within the receptor protein. It causes a change in shape, which results in a change for the cell. That effect varies as much as hormones do; commonly there is a signal produced inside the cell by the hormone binding on the outside of the cell.

COMMUNICATION MATTERS

Back to our investigation of membrane proteins and their important role in nerve signal transmission. We so far have covered how a sensory signal travels from a client’s big toe through a wave of membrane depolarization, which is called an action potential. The action potential is what moves up the axon, past the cell body of the nerve cell to the exact opposite end of the nerve cell from which the message started. Once at that cell’s terminus, a hormone communication takes place.

At the end of the nerve cell carrying the signal, there are pockets of hormones found just beneath the surface of the membrane of this originating nerve cell. These pockets are bound by their own phospholipids membrane and hold a high concentrationof the hormone acetylcholine, approximately 10,000 molecules per vesicle. When that depolarized action potential reaches this nerve cell terminus, it activates these vesicles to release their hormone contents to the outside of the cell.

Conveniently, there is the beginning of another nerve cell very close to this terminus. In fact, the space between the two is called the synaptic cleft. Once the hormone acetylcholine has been released into the synaptic cleft, it binds to the receptor found on the membrane surface of the next nerve cell.

In this particular case, when the hormone binds, a change is initiated in the receptor hormone, which opens a pore within that protein. As might be expected, that pore opening is a built in ion channel, which begins the depolarization of this new nerve cell. This is how the signal gets propagated between two nerve cells. The action potential continues down this new nerve cell in the same manner as before, opening ion channels along the way and resetting them with the ion pump. Incidentally, as quick as that acetylcholine is dumped out into the synaptic cleft space, it is taken back up by other proteins designed for that function.

MEMBRANES ARE LIFE

This has been an introduction to the molecular view of cellular membranes. The complexity does expand from this discussion. Of note, cells have their exterior membranes as mentioned; they also have many membranes inside the cell as well. Cells have organelles, which are all distinguished by internal membranes. For example, the nucleus is a membrane surrounding the DNA of the cell, with specific and specialized membrane proteins only found in nuclear membranes. Mitochondria actually have two membranes to complete their function of cellular respiration. There are many varying vesicles depending on the cell type at hand. This only really begins to describe how important membranes are to the inside function of cellular life.

When we touch our clients, we are touching their membranes; we are affecting the fluids of their cellular world – both inside and outside the cell. In fact, this is where our hands are working. It is important that we have awareness around the truth behind these physical molecular structures and their dynamic nature as we strive to describe what Rolfing is.

REFERENCES

Alberts, B., et al., Molecular Biology of the Cell, 3rd ed., Garland Publishing Inc., New York & London, 1994.

Juhan, Deane, Job’s Body: A Handbook for Bodyworkers, Station Hill Barrytown Ltd., 1998.Insane in the Membrane